Single-cell transcriptomic analysis identifies an immune erythroid in paroxysmal nocturnal hemoglobinuria

Introduction: PNH is complement mediated intravascular hemolysis, the mechanism of intrinsic immune-like transcriptional programs within erythroid remains unclear. Methods Bone marrow samples were collected from patients with PNH and healthy controls. CD59-/+ cells were isolated for single-cell sequencing analysis, based on differential gene markers, erythroid cells were classified into six groups. Results Functional analysis revealed that groups C0, C1, C4, and C5 were primarily enriched in co-translational proteins that target the membrane, RNA catabolic processes, ribonucleoprotein complex biogenesis, and ATP metabolic process pathways. Groups C3 and C6 were associated with T-cell activation and antigen processing. Further investigation of groups C3 and C6 revealed that upregulated genes in the positive cells of PNH are enriched in immune-related pathways. Subsequent cross-enrichment analysis using immune and GEO databases identified five genes, namely AHNAK, CCL5, IL32, CD3E, and IL2RG, that may play a role in this process. Our analysis revealed a correlation between mRNA levels of IL32, IL2RG, CD3E, and CCL5 in the CD235a-positive cells of patients and their immunological markers. Conclusion A subset of erythroid cells with immune functions was identified in PNH, and gene upregulation was predominantly observed in CD59 + cells. We examined five genes which may play a role in this process and may offer novel insights for future investigations.